Deoxy‐nitrosugars 12th communication Synthesis of isosteric mono‐phosphonate analogues of β‐and α‐ D ‐fructose 2,6‐bisphosphate

A synthesis of the isosteric mono‐phosphonate analogues 2a and 19 of the β‐and α‐D‐fructose 2,6‐bisphosphate, respectively, is described. Chain elongation of the 1‐deoxy‐1‐nitro‐D‐arabinose 3 (Scheme 1) by a Henry reaction with paraformaldehyde followed by protection of the resulting alcohol (methoxymethyl ether) and a radical‐chain substitution by nitromethane anion gave the key intermediates, the gluco‐anhydroalditol 6 and the manno‐anhydroalditol 7. These products equilibrated under basic conditions. Conversion of 7 to the aldehyde 9, Abramov reaction of 9 with diphenyl phosphite followed by deoxygenation according to Barton gave the phosphonate 11 (Scheme 2). Selective hydrogenolysis of 11, phosphorylation and deprotection gave 2 which was converted to the tetrasodium salt 2a. Similarly, 6 was transformed into the isosteric phosphonate analogue 19 of the α‐D‐fructose 2,6‐bisphosphate (Scheme 3).